Cardiovascular disease remains the leading cause of death worldwide. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies aim largely to attenuate the pathological remodelling that occurs after injury and to reduce risk factors for cardiovascular disease. Studies in animal models indicate that transplantation of mesenchymal stem cells, bone-marrow-derived haematopoietic stem cells, skeletal myoblasts, or embryonic stem cells has the potential to improve the function of ventricular muscle after ischaemic injury. Clinical trials using primarily bone-marrow-derived cells and skeletal myoblasts have also produced some encouraging results. However, the current experimental evidence suggests that the benefits of cell therapy are modest, the generation of new cardiac tissue is low, and the predominant mechanisms of action of transplanted stem cells involve favourable paracrine effects on injured myocardium. Recent studies show that the adult heart possesses various pools of putative resident stem cells, raising the hope that these cells can be isolated for therapy or manipulated in vivo to improve the healing of cardiac muscle after injury. This article reviews the properties and potential of the various stem cell populations for cardiac repair and regeneration as well as the barriers that might lie ahead.